Evidence-based medicine, statistics and pharmacy practice

Adam La Caze

PHRM1102 W3 Workshop

Learning outcomes (Module)

  1. Apply skills in evidence-based practice to addressing therapeutic questions [Pharmacy]
  2. Evaluate the strengths and weaknesses of key pharmacy resources for addressing therapeutic questions [Pharmacy]
  3. Be able to interpret and explain common measures of effect from clinical studies [Pharmacy]
  4. Be able to describe (in general terms) the logic of statistical inference (including key concepts: p values, confidence intervals, power, type I and type II errors) [Statistics]
  5. Be able to identify different data types, common summary measures and and how they a represented [Statistics]
  6. Be able to describe key types of statistical tests [Statistics]
  7. Be able to read health research (specifically randomized trials of pharmaceuticals) and identify the primary statistical hypothesis, PICO, the study type, the measure of effect (ratio, difference; relative, absolute) and the meaning of the statistical result [Pharmacy + Statistics]

Learning outcomes (W3)

  1. Explain how we determine whether or not drugs work
  2. Discuss the strengths and limitations of common study designs in clinical epidemiology
  3. Summarize an interventional study in the PICO format (participants, intervention, comparator, outcome)

Engagement tasks

Summarise the following studies in PICO form:

  • Williams, C. M., et al. (2014). Efficacy of paracetamol for acute low-back pain: A double-blind, randomised controlled trial. The Lancet, 384(9954), 1586–1596. https://doi.org/10.1016/S0140-6736(14)60805-9

  • Roman-Blas, J. A., et al. (2017). Combined Treatment With Chondroitin Sulfate and Glucosamine Sulfate Shows No Superiority Over Placebo for Reduction of Joint Pain and Functional Impairment in Patients With Knee Osteoarthritis: A Six-Month Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis and Rheumatology, 69(1), 77–85. https://doi.org/10.1002/art.39819

Questions?

  • Ivermectin (types of evidence)
  • Random and systematic error (adherence study)
  • HRT and cardiovascular disease (bias, confounders, randomised trials)
  • Randomized trial for AstraZeneca Covid-19 vaccine (PICO)

What works?

What works?

How would you determine whether homeopathy works?

Information about homeopathy

Evidence See National Health and Medical Research Council (2015).

Study design

Tea-drinker

You know a tea drinker who believes they can tell whether or not milk was added before the tea.

Design a simple study to determine whether this is true.

Coin of unknown bias

You have a coin that you suspect may not be fair (i.e. the chance of Heads on any one toss might not be half).

Design a simple study to determine whether the coin is fair.

Why randomised trials?

Why randomised trials

  • Minimise the effect of confounders on the assessment of whether a treatment works

    • Random allocation is superior to alternatives in providing groups in which confounders are (roughly) evenly distributed (whether known or unknown)

  • Random allocation aids statistical analysis

  • Prospective (randomised) studies permit the use of additional methods to reduce bias (masking and appropriate control)

Why cohort and case control studies?

Why cohort and case control studies

  • de Abajo et al. (1999) conducted a case control study to first identify an association between SSRIs, NSAIDs and gastrointestinal bleeding

  • The investigators reviewed 1899 cases of upper gastrointestinal bleeding or ulcer perforation

  • 10,000 controls were matched for age, sex and year that the case was identified

  • SSRI users were more likely to experience upper GI bleeding (adjusted relative risk 3.0, 95% CI 2.1–4.4)

  • SSRI users taking NSAIDs were much more likely to experience upper GI bleeding (adjusted relative risk 15.6, 95% CI 6.6–36.6)

PICO

PICO

PICO Clinical Question Critical Appraisal
Participants What are the key characteristics of the patient(s) Who was recruited to the study? What were the inclusion/exclusion criteria? Who participated?
Intervention What is the intervention under consideration What intervention did the treatment group receive?
Comparator What is the comparator, control, or usual alternative What did the control or placebo group receive?
Outcome What is the patient-relevant outcome? (or society-relevant outcome?) What was the primary outcome of the trial?

AZ Covid-19 vaccine

PICO for Voysey et al. (2021)
PICO Notes
Participants Participants of one of four vaccine RCTs. Most participants were adults in professions at risk of Covid-19.
Intervention Two doses of AZ-Oxford vaccine
Comparator Control: meningococcal vaccine or saline
Outcome Virologically confirmed, symptomatic Covid-19 (NAAT-positive swab, plus fever, cough, shortness of breath or anosmia or ageusia

Primary endpoint and analysis plan

The primary outcome was virologically confirmed, symptomatic COVID-19, defined as a NAAT-positive swab combined with at least one qualifying symptom (fever \(\ge\) 37.8°C, cough, shortness of breath, or anosmia or ageusia (103)

… each study had to meet prespecified criteria of having at least five cases eligible for inclusion in the primary outcome before a study was included in efficacy analyses (103)

Vaccine efficacy was calculated as 1 – adjusted relative risk (ChAdOx1 nCoV-19 vs control groups) computed using a Poisson regression model with robust variance (103)

Outcome

There were 30 (0.5%) cases among 5807 participants in the vaccine arm and 101 (1.7%) cases among 5829 participants in the control group, resulting in vaccine efficacy of 70.4% (95.8% CI 54.8–80.6; table 2; figure).

References

de Abajo, F. J., Rodríguez, L. A., & Montero, D. (1999). Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. British Medical Journal (Clinical Research Ed.), 319(7217), 1106–1109. https://doi.org/10.1136/bmj.319.7217.1106

National Health and Medical Research Council. (2015). Evidence on the effectiveness of homeopathy for treating health conditions (pp. 1–301). NHMRC. https://www.nhmrc.gov.au/about-us/resources/homeopathy

Voysey, M., Clemens, S. A. C., Madhi, S. A., Weckx, L. Y., Folegatti, P. M., Aley, P. K., Angus, B., Baillie, V. L., Barnabas, S. L., Bhorat, Q. E., & others. (2021). Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The Lancet, 397(10269), 99–111.